Apparatus and methods for preparative liquid chromatography

Abstract

A method of liquid chromatography includes providing one or more solvent reservoirs, providing a solvent pump, drawing one or more solvents into the pump in response to a pressure drop that promotes outgassing of the solvents, and dispersing outgassed bubbles into smaller bubbles to promote re-dissolution of the gas. A liquid-chromatography apparatus includes at least two solvent reservoirs, a pump, at least one bubble-dispersing unit that receives a pressurized flow of proportioned solvents from the pump, and a control unit. The control unit includes a processor and a memory that stores instructions; the control unit controls proportioning of solvents to obtain a preselected solvent composition, and pumping at flow rates to support preparative-scale or process-scale liquid chromatography.

What is claimed is: 
     
       1. A liquid-chromatography apparatus, comprising:
 at least two solvent reservoirs respectively containing a first solvent and a second solvent, which each contain dissolved gas; 
 a gradient proportioning valve in fluid communication with the at least two solvent reservoirs; 
 a pump comprising at least two pistons disposed in respective chambers in parallel or serial fluid communication with an outlet of the gradient proportioning valve to receive a flow of proportioned solvents from the gradient proportioning valve; 
 at least one bubble-dispersing unit in fluid communication with the pump to receive a pressurized flow of proportioned solvents from the pump and to disperse bubbles in the flow; and 
 a control unit, in communication with the pump and the gradient proportioning valve, and comprising at least one processor and at least one memory for storing a plurality of instructions, which, when executed by the at least one processor, causes implementation of the steps of, 
 repeatedly switching the gradient proportioning valve to provide the proportioned solvents in association with a preselected solvent composition, and 
 drawing the selected solvent mixture into the pump at a flow rate of at least 5 ml/min. 
 
     
     
       2. The apparatus of  claim 1 , wherein the at least one bubble-dispersing component is disposed at an output port of the pump. 
     
     
       3. The apparatus of  claim 1 , further comprising a solvent mixer in fluid communication with the pump to receive the pressurized flow of proportioned solvents from the pump, wherein the at least one bubble-dispersing component is disposed in a flow path closer to an outlet port of the mixer than to an inlet port of a separation column. 
     
     
       4. The apparatus of  claim 3 , wherein the at least one bubble-dispersing component is disposed at the output port of the mixer. 
     
     
       5. The apparatus of  claim 1 , wherein the first solvent comprises water and the second solvent comprises methanol. 
     
     
       6. The apparatus of  claim 1 , wherein the apparatus does not include a vacuum degasser. 
     
     
       7. The apparatus of  claim 1 , wherein each of the chambers have a chamber volume in a range of 0.5 ml to 2 ml. 
     
     
       8. The apparatus of  claim 1 , wherein the bubble-dispersing component comprises a mesh or a porous material. 
     
     
       9. The apparatus of  claim 1 , wherein the plurality of instructions further cause implementation of the step of providing the pressurized flow of proportioned solvents from the pump at a pressure of at least 500 pounds per square inch. 
     
     
       10. The apparatus of  claim 1 , further comprising an injector for injecting a sample into the flow of proportioned solvents,
 wherein the bubble-dispersing unit is disposed upstream of the injector. 
 
     
     
       11. The apparatus of  claim 10 , wherein the at least one bubble-dispersing component is disposed at an output port of the pump. 
     
     
       12. The apparatus of  claim 10 , further comprising a solvent mixer in fluid communication with the pump to receive the pressurized flow of proportioned solvents from the pump, wherein the at least one bubble-dispersing component is disposed in a flow path closer to an outlet port of the mixer than to an inlet port of a separation column.